JunD mediates androgen‐induced oxidative stress in androgen dependent LNCaP human prostate cancer cells

Abstract

Based on these data, we conclude that JunD is an essential mediator of the androgen-induced increase in ROS levels in LNCaP cells.

JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-β (TGF-β)-induced Inhibition of Cell Proliferation

“…Interestingly, this action of JunD on prostate cancer cell migration was reported to be opposite to the effect of JunB and c-Jun (73). JunD plays important regulatory roles in both androgen-dependent and androgen-independent prostate cancer cells by functioning as a co-activator for the androgen receptor to mediate androgen-induced oxidative stress in LNCaP cells (51,74) or by interacting with the NFB pathway to induce IL-6, an important mediator of metastatic, hormone-refractory prostate cancer (75). On the other hand, Church et al (50) reported that cell growth inhibition in LNCaP cells after treatment with androgens resulted in a concomitant increase in JunD expression.…”

“…In a recent report, JunB was shown to play an important role in maintaining cell senescence that blocks malignant prostate cell transformations (48) and has been shown to be a potent activator of KAI1 (49). Jun proteins by themselves or in combination with members of the Fos proteins have also been implicated in the actions of androgens (50,51), atmospheric pollutants (52), growth factors (53), phytochemicals (54 -56), peroxides (57), isothiocyanates (58), glycoproteins (59), and, most recently, proteasome inhibitors (60). AP-1 proteins form multiple homo-and heterodimers, and the composition of these dimers may dictate expression of specific genes involved in specific biological responses.…”

Polyamines Regulate the Stability of JunD mRNA by Modulating the Competitive Binding of Its 3′ Untranslated Region to HuR and AUF1

“…Although c-Jun and JunB behave as immediate-early response genes and enhance the G 1 -to-S-phase transition upon mitogenic stimulation, the overexpression of JunD inhibits cell proliferation (14,29,38). JunD also regulates the expression of genes involved in antioxidant defense and hydrogen peroxide production (10,26,37) and reduces tumor angiogenesis by repressing vascular endothelial growth factor transcription (3,10). Mice lacking JunD exhibit multiple defects in their reproductive system (47), enhanced cardiomyocyte apoptosis and hypertrophic growth (15), chronic kidney disease (42), and increased bone formation (20).…”

Novel Inhibitors of Protein-Protein Interaction for Prostate Cancer Therapy

“…We chose the compounds to be tested in the full series of ROS and growth cell culture studies based on percent inhibition of the AR-JunD interaction by the compounds in the HTS assay: 7 of the 12 non-antiandrogenic compounds were selected for these studies based on ≥ 50% inhibition of AR-JunD in the HTS. DCF and DNA assays were used to measure the amount of ROS production and growth, respectively, in both androgen-dependent LNCaP and androgenindependent LNCaP C4-2 cell lines following our established methods [2][3][4]. Two compounds, GWARJD10-001 and GWARJD14-001, showed significant activity against androgen-induced ROS production and AD growth in LNCaP cells as well as LNCaP C4-2 AI growth.…”